Rare coding variants involving MYO7A and other genes encoding stereocilia link proteins in familial meniere disease
Identificadores
URI: http://hdl.handle.net/10481/70662Metadatos
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ELSEVIER
Materia
Genomics Hearing loss Inner ear Meniere’s disease Vestibular disorders
Fecha
2021Referencia bibliográfica
Rare coding variants involving MYO7A and other genes encoding stereocilia link proteins in familial meniere disease. Hearing Research 409 (2021) 108329, https://doi.org/10.1016/j.heares.2021.108329
Resumen
The MYO7A gene encodes a motor protein with a key role in the organization of stereocilia in auditory
and vestibular hair cells. Rare variants in the MYO7A (myosin VIIA) gene may cause autosomal dominant
(AD) or autosomal recessive (AR) sensorineural hearing loss (SNHL) accompanied by vestibular dysfunction or retinitis pigmentosa (Usher syndrome type 1B). Familial Meniere’s disease (MD) is a rare inner
ear syndrome mainly characterized by low-frequency sensorineural hearing loss and episodic vertigo associated with tinnitus. Familial aggregation has been found in 6–8% of sporadic cases, and most of the
reported genes were involved in single families. Thus, this study aimed to search for relevant genes not
previously linked to familial MD. Through exome sequencing and segregation analysis in 62 MD families,
we have found a total of 1 novel and 8 rare heterozygous variants in the MYO7A gene in 9 non-related
families. Carriers of rare variants in MYO7A showed autosomal dominant or autosomal recessive SNHL
in familial MD. Additionally, some novel and rare variants in other genes involved in the organization
of the stereocilia links such as CDH23, PCDH15 or ADGRV1 co-segregated in the same patients. Our findings reveal a co-segregation of rare variants in the MYO7A gene and other structural myosin VIIA binding
proteins involved in the tip and ankle links of the hair cell stereocilia. We suggest that recessive digenic
inheritance involving these genes could affect the ultrastructure of the stereocilia links in familial MD